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Following radiation induced DNA damage, several repair pathways are activated to help preserve genome integrity. Double Strand Breaks (DSBs), which are highly toxic, have specified repair pathways to address them. The main repair pathways used to resolve DSBs are Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR). Cell cycle phase determines the availability of HR, but the repair choice between pathways in the G2 phases where both HR and NHEJ can operate is not clearly understood. This study compares several in silico models of repair choice to experimental data published in the literature, each model representing a different possible scenario describing how repair choice takes place. Competitive only scenarios, where initial protein recruitment determines repair choice, are unable to fit the literature data. In contrast, the scenario which uses a more entwined relationship between NHEJ and HR, incorporating protein co-localisation and RNF138-dependent removal of the Ku/DNA-PK complex, is better able to predict levels of repair similar to the experimental data. Furthermore, this study concludes that co-localisation of the Mre11-Rad50-Nbs1 (MRN) complexes, with initial NHEJ proteins must be modeled to accurately depict repair choice.
|Early online date||23 Apr 2019|
|Publication status||Published - 23 Apr 2019|
FingerprintDive into the research topics of 'Mechanistic modelling supports entwined rather than exclusively competitive DNA double-strand break repair pathway'. Together they form a unique fingerprint.
- 2 Finished
Grand Challenge Network in Network+ in Proton Therapy.
1/05/16 → 31/10/21
Global Challenge Network + in Advanced Radiotherapy.
Kirkby, K., Illidge, T., Kirkby, N., Mackay, R., Merchant, M. & Owen, H.
1/07/15 → 30/06/21